Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking

Neuron. 2006 Nov 9;52(3):445-59. doi: 10.1016/j.neuron.2006.08.033.


Arc/Arg3.1 is an immediate-early gene whose mRNA is rapidly transcribed and targeted to dendrites of neurons as they engage in information processing and storage. Moreover, Arc/Arg3.1 is known to be required for durable forms of synaptic plasticity and learning. Despite these intriguing links to plasticity, Arc/Arg3.1's molecular function remains enigmatic. Here, we demonstrate that Arc/Arg3.1 protein interacts with dynamin and specific isoforms of endophilin to enhance receptor endocytosis. Arc/Arg3.1 selectively modulates trafficking of AMPA-type glutamate receptors (AMPARs) in neurons by accelerating endocytosis and reducing surface expression. The Arc/Arg3.1-endocytosis pathway appears to regulate basal AMPAR levels since Arc/Arg3.1 KO neurons exhibit markedly reduced endocytosis and increased steady-state surface levels. These findings reveal a novel molecular pathway that is regulated by Arc/Arg3.1 and likely contributes to late-phase synaptic plasticity and memory consolidation.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / metabolism
  • Animals
  • Animals, Newborn
  • Blotting, Western / methods
  • Cells, Cultured
  • Cytoskeletal Proteins / physiology*
  • Dynamins / metabolism
  • Endocytosis / physiology*
  • Hippocampus / cytology
  • Immunohistochemistry / methods
  • Immunoprecipitation / methods
  • Microscopy, Immunoelectron / methods
  • Models, Neurological
  • Nerve Tissue Proteins / physiology*
  • Neurons / physiology
  • Neurons / ultrastructure
  • Protein Binding / physiology
  • Protein Transport / physiology
  • Rats
  • Receptors, AMPA / metabolism*
  • Synaptosomes / metabolism
  • Transfection / methods
  • Two-Hybrid System Techniques


  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • Receptors, AMPA
  • activity regulated cytoskeletal-associated protein
  • Acyltransferases
  • Dynamins